title: Deficient CEBPA DNA binding function in normal karyotype AML patients is associated with favorable prognosis.
abstract: CCAAT/enhancer binding protein-α (CEBPA) mutations in acute myeloid leukemia (AML) patients with a normal karyotype (NK) confer favorable prognosis, whereas NK-AML patients per se are of intermediate risk. This suggests that blocked CEBPA function characterizes NK-AML with favorable outcome. We determined the prognostic significance of CEBPA DNA binding function by enzyme-linked immunosorbent assay in 105 NK-AML patients. Suppressed CEBPA DNA binding was defined by 21 good-risk AML patients with inv(16) or t(8;21) (both abnormalities targeting CEBPA) and 8 NK-AML patients with dominant-negative CEBPA mutations. NK-AML patients with suppressed CEBPA function showed a better overall survival (P = .0231) and disease-free survival (P = .0069) than patients with conserved CEBPA function. Suppressed CEBPA DNA binding was an independent marker for better overall survival and disease-free survival in a multivariable analysis that included FLT3-ITD, NPM1 and CEBPA mutation status, white blood cell count, age and lactate dehydrogenase. These data indicate that suppressed CEBPA function is associated with favorable prognosis in NK-AML patients.
authors.affiliation: Department of Internal Medicine and Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: José
authors.initials: J
authors.lastname: Fos
authors.forename: Thomas
authors.initials: T
authors.lastname: Pabst
authors.forename: Vibor
authors.initials: V
authors.lastname: Petkovic
authors.forename: Daniel
authors.initials: D
authors.lastname: Ratschiller
authors.forename: Beatrice U
authors.initials: BU
authors.lastname: Mueller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D020298:U937 Cells; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; C095514:CBFbeta-MYH11 fusion protein; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; C000716967:NPM1 protein, human; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein; D000090243:Nucleophosmin